Exploring the trifluoromenadione core as ...
Document type :
Article dans une revue scientifique
DOI :
Permalink :
Title :
Exploring the trifluoromenadione core as a template to design antimalarial redox-active agents interacting with glutathione reductase
Author(s) :
Belorgey, Didier [Auteur]
École Européene de Chimie, Polymères et Matériaux de Strasbourg [ECPM]
Müller, Tobias [Auteur]
Heidelberg University
Vezin, Herve [Auteur]
Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement (LASIRE) - UMR 8516
Lanzer, Michael [Auteur]
Heidelberg University Hospital [Heidelberg]
Davioud-Charvet, Elisabeth [Auteur]
École Européene de Chimie, Polymères et Matériaux de Strasbourg [ECPM]
École Européene de Chimie, Polymères et Matériaux de Strasbourg [ECPM]
Müller, Tobias [Auteur]
Heidelberg University
Vezin, Herve [Auteur]

Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement (LASIRE) - UMR 8516
Lanzer, Michael [Auteur]
Heidelberg University Hospital [Heidelberg]
Davioud-Charvet, Elisabeth [Auteur]
École Européene de Chimie, Polymères et Matériaux de Strasbourg [ECPM]
Journal title :
Organic & Biomolecular Chemistry
Abbreviated title :
Org. Biomol. Chem.
Volume number :
10
Pages :
4795-4808
Publisher :
Royal Society of Chemistry (RSC)
Publication date :
2012
ISSN :
1477-0539
HAL domain(s) :
Chimie/Chimie théorique et/ou physique
English abstract : [en]
Menadione is the 2-methyl-1,4-naphthoquinone core used to design potent antimalarial redox-cyclers to affect the redox equilibrium of Plasmodium-infected red blood cells. Exploring the reactivity of fluoromethyl-1,4-naph ...
Show more >Menadione is the 2-methyl-1,4-naphthoquinone core used to design potent antimalarial redox-cyclers to affect the redox equilibrium of Plasmodium-infected red blood cells. Exploring the reactivity of fluoromethyl-1,4-naphthoquinones, in particular trifluoromenadione, under quasi-physiological conditions in NADPH-dependent glutathione reductase reactions, is discussed in terms of chemical synthesis, electrochemistry, enzyme kinetics, and antimalarial activities. Multitarget-directed drug discovery is an emerging approach to the design of new antimalarial drugs. Combining in one single 1,4-naphthoquinone molecule, the trifluoromenadione core with the alkyl chain at C-3 of the known antimalarial drug atovaquone, revealed a mechanism for CF3 as a leaving group. The resulting trifluoromethyl derivative 5 showed a potent antimalarial activity per se against malarial parasites in culture.Show less >
Show more >Menadione is the 2-methyl-1,4-naphthoquinone core used to design potent antimalarial redox-cyclers to affect the redox equilibrium of Plasmodium-infected red blood cells. Exploring the reactivity of fluoromethyl-1,4-naphthoquinones, in particular trifluoromenadione, under quasi-physiological conditions in NADPH-dependent glutathione reductase reactions, is discussed in terms of chemical synthesis, electrochemistry, enzyme kinetics, and antimalarial activities. Multitarget-directed drug discovery is an emerging approach to the design of new antimalarial drugs. Combining in one single 1,4-naphthoquinone molecule, the trifluoromenadione core with the alkyl chain at C-3 of the known antimalarial drug atovaquone, revealed a mechanism for CF3 as a leaving group. The resulting trifluoromethyl derivative 5 showed a potent antimalarial activity per se against malarial parasites in culture.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
CNRS
CNRS
Collections :
Submission date :
2021-06-17T15:31:12Z
2021-10-05T11:03:15Z
2021-10-05T11:03:15Z